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J. Biol. Chem., Vol. 283, Issue 13, 8301-8309, March 28, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/13/8301    most recent M706730200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bae, G.-U. Articles by Krauss, R. S. Search for Related Content PubMed PubMed Citation Articles by Bae, G.-U. Articles by Krauss, R. S. Social Bookmarking                      What's this?

Regulation of Myoblast Motility and Fusion by the CXCR4-associated Sialomucin, CD164^*

Gyu-Un Bae¹, Ursula Gaio², Youn-Joo Yang, Hye-Jin Lee, Jong-Sun Kang³, and Robert S. Krauss⁴

From the Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York 10029 and the Samsung Biomedical Research Institute, SungKyunKwan University School of Medicine, Suwon 440-746, South Korea

Myoblast fusion is fundamental to the development and regeneration of skeletal muscle. To fuse, myoblasts undergo cell-cell recognition and adhesion and merger of membranes between apposing cells. Cell migration must occur in advance of these events to bring myoblasts into proximity, but the factors that regulate myoblast motility are not fully understood. CD164 is a cell surface sialomucin that is targeted to endosomes and lysosomes via its intracellular region. In hematopoietic progenitor cells, CD164 forms complexes with the motility-stimulating chemokine receptor, CXCR4, in response to the CXCR4 ligand, CXCL12/SDF-1 (Forde, S., Tye, B. J., Newey, S. E., Roubelakis, M., Smythe, J., McGuckin, C. P., Pettengell, R., and Watt, S. M. (2007) Blood 109, 1825–1833). We have previously shown that CD164 stimulates myotube formation in vitro. We report here that CD164 is associated with CXCR4 in C2C12 myoblasts. Cells in which CD164 levels are increased or decreased via overexpression or RNA interference-mediated knockdown, respectively, show enhanced or reduced myotube formation and cell migration, the latter both basally and in response to CXCL12/SDF-1. Furthermore, expression of CD164 cytoplasmic tail mutants that alter the endosome/lysosome targeting sequence and, consequently, the subcellular localization in myoblasts, reveals a similar correlation between cell motility and myotube formation. Finally, Cd164 mRNA is expressed in the dorsal somite (the early myogenic compartment of the mouse embryo) and in premuscle masses. Taken together, these results suggest that CD164 is a regulator of myoblast motility and that this property contributes to its ability to promote myoblast fusion into myotubes.

Received for publication, August 13, 2007 , and in revised form, January 24, 2008.

^* This work was funded in part by National Institutes of Health Grant AR050403. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains two supplemental figures.

¹ Present address: Samsung Biomedical Research Institute, SungKyunKwan University School of Medicine, Suwon 440-746, South Korea.

² Present address: National Research Center for Environment and Health, Institute of Stem Cell Research, Neuherberg 85764, Germany.

³ Supported by the T. J. Martell Foundation.

⁴ To whom correspondence should be addressed: Box 1020, Mount Sinai School of Medicine, New York, NY 10029. Fax: 212-860-9274; E-mail: Robert.Krauss{at}mssm.edu.

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